The following studies are planned: 1) Characterization of the NADPH-dependent iodotyrosine deiodinating system in bovine thyroid particulate fractions with special reference to the roles of ferredoxin and ferrodoxin reductase in electron transfer from NADPH to the substrate. 2) Purification and characterization of thyroid ferredoxin reductase from bovine thyroid mitochondria and microsomes and its relation to the previously characterized steapsin-solubilized dithionite-responsive iodotyrosine deiodinase. 3) Studies on the state of activation of calmodulin in adipocytes, erythrocytes and liver in relation to thyroid status by measurements of (a) (Ca2 ion plus Mg2 ion) ATPase activities in erythrocyte membranes and subcellular fractions of liver and (b) phosphodiesterase activities in the various subcellular fractions of liver and adipocytes. Tissues from hyper-, eu-, and hypo-thyroid rats will be used. 4) Purification of membrane-bound T4 5'-deiodinase with emphasis on 1) reconstitution of the enzymatic activity of the lipid-depleted enzyme with appropriate cofactors; 2) development of a more rapid assay for the enzyme during purification; 3) specific, reversible isotope (35S) labeling of the enzyme to allow detection without assay. 5) Studies on the interrelationship between T4 and rT3 5'-deiodination with particular reference to the inhibitory effects of rT3 on T3 formation and the kinetics of thiol activation of outer-ring deiodination of T4 and rT3.